Devices for the automated release of liquid medicaments normally are used with patients who have a continuous need for a medicine that can be administered by subcutaneous infusion, which need can vary in the course of the day. Example applications for computer-controlled infusion pump devices, such as insulin pumps, include certain pain therapies and the treatment of diabetes. Such devices can be carried by a patient on the body and can contain a certain amount of liquid medicament in a medicine reservoir in the form of a container. The medicine reservoir often comprises medicine sufficient for one or several days. The liquid medicament is supplied to the patient's body from the medicine reservoir through an infusion cannula or an injection needle.
Convenience and discretion are paramount concerns for patients who may self-administer medicaments, for example, insulin, by means such as an infusion pump. Consequently, the dimensions of such infusion devices must be limited, and particularly the overall length should be as small as possible to prevent the devices from being evident through clothing and to allow the patient to carry the devices as comfortably as possible.
In the interest of maintaining sterility and preventing contamination, typically the devices are single-use devices. Alternatively, the devices or parts of the devices can be reused by the patient, for example, by replacing an empty medicament container or by refilling the container. The refilling of containers has the advantage that medicaments that are not readily available in pre-filled containers can be used for such infusion pump devices, thereby providing the patient with a larger choice of sources for delivery of the medicaments.
Standard infusion pump devices that are carried on or near the body have a medicine reservoir with a cylindrical ampoule and a displacement piston. The piston is pushed into the ampoule by a piston rod or a threaded spindle to convey the liquid medicament. These known designs are undesirably long or thick and do not provide advantageously compact infusion pumps.
Manufacturers try to meet the demand of small infusion pump devices by various means. For example, the infusion pump can be divided into structural assemblies arranged in separate, smaller housings that can joined by a wireless or a wired connection. An example of such a modular infusion pump device is disclosed in U.S. 2006/0184119 A1.
Another possibility is the use of particularly flat containers. For example, the cylindrical ampoule may be replaced by a container having a rectangular or other suitable cross-section and may interact with a displacement piston of a corresponding shape. Different embodiments of such compact medicine reservoir devices are shown in WO 2008/122135 A1.
A further approach to reduce the overall volume of an infusion device is to replace the syringe-type dosing mechanism with a downstream pump system. In the syringe-type dosing mechanism, an actuator displaces a piston along a long axis of a container to convey the appropriate amount of liquid medicine. In the device with a downstream pump system, a miniaturized pump downstream of the reservoir causes a negative pressure-gradient that conveys the product from the reservoir to its destination. An example of such a pump is described in WO 2004/009162 A1.
For some of the abovementioned infusion devices, the pressure gradient achievable with the pump system is not very high. A suitable container for such devices is disclosed in U.S. 2007/0123820 A1, comprising a flat container and a flat piston body arranged in the body in a sliding manner. Fully filled, such a container has a ratio of maximum height to overall width of less than 1.25. The cross-sectional area of the container in relation to the displacement axis is much larger than for conventional cylinder-piston arrangements. Even a comparably small pressure gradient generated by a miniaturized pump can overcome the friction force of the piston seal as the piston glides on the inner wall of the container.
In an especially advantageous approach the rigid container and movable piston are replaced by a flexible container. Such a flexible container may comprise, for example, two flexible-wall sheets that are sealed together.
One type of infusion pump device with a flexible container is disclosed in U.S. 2007/0049865 A1. The flexible container comprises a front and rear wall sheet sealed together, and a port that is centrally arranged on one of the wall sheets. The port comprises a septum and a flange sealed onto the sheet material. A hollow needle penetrates the septum, thereby connecting the container to the infusion cannula. The flexible container containing the liquid medicament is arranged in a second, rigid, fluid-filled container in fluid communication with a primary reservoir of a hydraulic fluid through a conduit comprising a flow restrictor. The primary reservoir is essentially a cartridge with a moveable piston. A spring is arranged to act on the piston to drive fluid from the reservoir to the second container, thereby expelling medicament from the flexible container when the latter is connected to an infusion needle. The flow rate is determined by the pressure generated in the drive fluid, the viscosity of the drive fluid, and the flow resistance in the flow restrictor. Because the contained cannot be refilled, the device is intended for single use. Also, both the hydraulic fluid piston and the second, rigid container increase the total volume of the device. Furthermore, the indirect pumping method complicates the construction of the device and limits the dosing accuracy. Such an infusion pump device thus is not suitable for dosing-critical applications such as the administration of insulin to a diabetes patient.
A common problem of flexible containers with ports as used, for example, in IV bags, is the dead volume resulting between the collapsed container and the port. Dead volume cannot be used, meaning that it cannot be emptied. Thus, flexible containers are impossible to completely drain. Though dead volumes are of minor concern for larger flexible containers of 100 mL or more, such as those used, for example, for blood preservations, nutritional fluids, or intravenous infusions, the loss of useable container volume is of considerably higher concern with smaller containers suitable for infusion pumps having a total volume of only 5 mL or less. In addition, the concentration of the medicament may be much higher than in an intravenous solution container, which further increases the negative effect of the dead volume. In addition to the increased costs, the dead volume leads also to an increase of the overall volume of the flexible container, and thus of the volume of an infusion pump device comprising such a flexible container.
For single-use containers filled with the medicament, the dead volume increases the effective costs per dose and thus of the overall therapy costs, because a certain percentage of the medicament inevitably will remain in the container and will be wasted. This cost effect is especially important for expensive medicaments.
If a container is provided empty, intended to be filled with the appropriate medicament by the user, the dead volume initially is filled with air. If the air remains in the container it may lead to potentially dangerous dosing errors. Furthermore, the administration of air into a patient's body should be avoided in some applications for medical reasons. However, removing the air from the container requires a certain skill of a user.
Another problem of flexible containers is the possibility that the container does not collapse homogeneously. Because the inner sides of the two wall sheets are pressed together by a pressure difference, parts of the container may be cut off from the port. Such constrictions are particularly problematic for very flexible materials with low elasticity. Other factors influencing the collapsing behavior of flexible containers include the shape and the size of a container, and the position of the port on the container.
Thus, there remains an ongoing need for improved flexible containers for storing medicaments.